OC-STAMP is a potential biomarker and therapeutic target for Silicosis: an exploratory investigation

Silicosis, a disease characterized by fibrous changes in lung tissue due to prolonged silica dust inhalation, exhibits a complex pathogenesis that remains inadequately addressed by current interventions. Although osteoclast stimulatory transmembrane protein (OC-STAMP) is implicated in Silicosis progression, its regulatory mechanisms are not fully understood. In this study, we detected elevated OC-STAMP expression in Silicosis patients and found that treatment with OC-STAMP siRNA can alleviate the progression of Silicosis in mice, suggesting the potential of OC-STAMP as a diagnostic and therapeutic target for Silicosis.

First, rat models of Silicosis were developed at various stages. A suite of histological and molecular techniques, including Hematoxylin and eosin (HE), Masson, Prussian blue staining, and immunohistochemistry, along with real-time polymerase chain reaction (RT-PCR), were employed to assess the expression levels of OC-STAMP, as well as indicators of  ferroptosis and fibrosis.Second, MLE-12 cells were cultured in vitro to establish an OC-STAMP overexpression model, and the relationship between OC-STAMP and ferroptosis was evaluated using flow cytometry, and western blotting. Subsequently, to verify the role of OC-STAMP and ferroptosis in Silicosis progression, we administered OC-STAMP siRNA and Fer-1 to Silicosis mice respectively. Whole-body volumetric plethysmography (WBP) was utilized to assess the respiratory function of the mice, and Micro-CT was applied to detect the lung nodules in the mice. The levels of OC-STAMP, as well as indexes associated with ferroptosis and fibrosis, were assessed using Hematoxylin and eosin (HE), Masson, Sirius red staining, immunohistochemistry, and western blot analysis. The polarization of macrophages towards M1 and M2 phenotypes in lung tissues was analyzed by flow cytometry. Ultimately, the plasma expression of OC-STAMP in patients diagnosed with Silicosis was quantified using enzyme-linked immunosorbent assay (ELISA).

In vivo experiments showed that OC-STAMP accelerates the fibrotic process of Silicosis, which may promote the epithelial-mesenchymal transformation by triggering ferroptosis of alveolar type II epithelial cells, and thus promote the progression of Silicosis. Furthermore, in vitro studies indicated that OC-STAMP overexpression causes ferroptosis in alveolar type II epithelial cells which contributes to fibrosis. Notably, treatment with siRNA in Silicosis mice confirmed that OC-STAMP inhibition effectively mitigates ferroptosis and retarded the progression of Silicosis fibrosis. Plasma of patients with Silicosis exhibited elevated OC-STAMP levels.

Overall, OC-STAMP induces ferroptosis and exacerbates fibrosis in Silicosis. OC-STAMP siRNA and Fer-1 mitigate abnormal collagen deposition and delay the progression of Silicosis. Collectively, these findings highlight the potential of OC-STAMP as a novel biomarker for diagnosing and treating Silicosis.